"Chip"ping away at heart failure.

Studies in the field of microarray technology have exploded onto the scene to delve into the unknown underlying mechanisms and pathways in molecular disease. Diseases of the cardiovascular system, particularly those with unexplained molecular etiologies, such as heart failure, have more recently been investigated using array technology. Our laboratory has sought to examine gene expression profiles of human heart failure using a 10,000+ element cardiovascular-based complementary DNA microarray constructed in-house, termed the "CardioChip.

Chromosomal distribution of the human cardiovascular transcriptome.

On the basis of previous observations in chromosomes 21 and 22, we hypothesize that there is a tissue-specific organization of cardiovascular gene transcripts in the human genome. To examine the distribution of heart-derived transcripts, we assigned a nonredundant set of 4628 fetal and 3574 adult known and uncharacterized cardiovascular expressed-sequence tags (cvESTs) to 5-Mb chromosomal 'windows' on the basis of publicly available sequence mapping data. On a whole-genome level (36,617 genes), chromosome 17 (19.

Global gene expression profiling of end-stage dilated cardiomyopathy using a human cardiovascular-based cDNA microarray.

To obtain a genomic portrait of heart failure derived from end-stage dilated cardiomyopathy (DCM), we explored expression analysis using the CardioChip, a nonredundant 10,848-element human cardiovascular-based expressed sequence tag glass slide cDNA microarray constructed in-house. RNA was extracted from the left ventricular free wall of seven patients undergoing transplantation, and five nonfailing heart samples. Cy3- and Cy5-labeled (and reverse dye-labeled) cDNA probes were synthesized from individual diseased or nonfailing adult heart RNA, and hybridized to the array.

Construction of a human cardiovascular cDNA microarray: portrait of the failing heart.

Identifying key genes that regulate the complex diseases of the cardiovascular system can be greatly facilitated with the use of microarrays. In an effort to obtain a global portrait of gene expression in the failing heart, we have constructed in-house a glass microscope slide cDNA microarray (termed "CardioChip") containing 10,368 redundant and randomly-selected sequenced expressed sequence tags (representing known genes, other matched ESTs, and novel, unmatched ESTs) derived from several human heart and artery cDNA libraries. From our preliminary data with Cy3- and Cy5-labeled probes, we have identified 38 transcripts showing a minimum twofold differential expression, among which are several novel or previously-uncharacterized genes.

Apoptosis-related genes expressed in cardiovascular development and disease: an EST approach.

Apoptosis (programmed cell death) is an important process which, in conjunction with cell proliferation, maintains cell number homeostasis. Although apoptosis has been more extensively investigated in other tissues [1,2], only recently has this process been suspected as a significant contributor to both disease and normal development of the cardiovascular system [3-6]. Grasping a comprehension of the underlying genetic mechanisms of apoptosis is especially crucial considering that cardiac myocytes irreversibly exit the cell cycle and thus fail to proliferate during pathological conditions.

A genome-based resource for molecular cardiovascular medicine: toward a compendium of cardiovascular genes.

Background: Large-scale partial sequencing of cDNA libraries to generate expressed sequence tags (ESTs) is an effective means of discovering novel genes and characterizing transcription patterns in different tissues. To catalogue the identities and expression levels of genes in the cardiovascular system, we initiated large-scale sequencing and analysis of human cardiac cDNA libraries.

Methods And Results: Using automated DNA sequencing, we generated 43,285 ESTs from human heart cDNA libraries.